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FMNL formins boost lamellipodial force generation

Author

Listed:
  • Frieda Kage

    (Zoological Institute, Technische Universität Braunschweig
    Molecular Cell Biology Group, Helmholtz Centre for Infection Research)

  • Moritz Winterhoff

    (Institute for Biophysical Chemistry, Hannover Medical School)

  • Vanessa Dimchev

    (Zoological Institute, Technische Universität Braunschweig
    Molecular Cell Biology Group, Helmholtz Centre for Infection Research)

  • Jan Mueller

    (Institute of Science and Technology Austria)

  • Tobias Thalheim

    (Soft Matter Physics Group, Institut für experimentelle Physik I, Leipzig University)

  • Anika Freise

    (Zoological Institute, Technische Universität Braunschweig
    Molecular Cell Biology Group, Helmholtz Centre for Infection Research)

  • Stefan Brühmann

    (Institute for Biophysical Chemistry, Hannover Medical School)

  • Jana Kollasser

    (Biomedical Institute, BRIC, University of Copenhagen
    Helmholtz Centre for Infection Research)

  • Jennifer Block

    (Molecular Cell Biology Group, Helmholtz Centre for Infection Research)

  • Georgi Dimchev

    (Zoological Institute, Technische Universität Braunschweig
    Molecular Cell Biology Group, Helmholtz Centre for Infection Research)

  • Matthias Geyer

    (Institute of Innate Immunity, University of Bonn)

  • Hans-Joachim Schnittler

    (Institute of Anatomy and Vascular Biology, Westfälische Wilhelms-Universität Münster)

  • Cord Brakebusch

    (Biomedical Institute, BRIC, University of Copenhagen)

  • Theresia E. B. Stradal

    (Helmholtz Centre for Infection Research)

  • Marie-France Carlier

    (Cytoskeleton Dynamics and Motility Group, Laboratoire d'Enzymologie et Biochimie Structurales)

  • Michael Sixt

    (Institute of Science and Technology Austria)

  • Josef Käs

    (Soft Matter Physics Group, Institut für experimentelle Physik I, Leipzig University)

  • Jan Faix

    (Institute for Biophysical Chemistry, Hannover Medical School)

  • Klemens Rottner

    (Zoological Institute, Technische Universität Braunschweig
    Molecular Cell Biology Group, Helmholtz Centre for Infection Research)

Abstract

Migration frequently involves Rac-mediated protrusion of lamellipodia, formed by Arp2/3 complex-dependent branching thought to be crucial for force generation and stability of these networks. The formins FMNL2 and FMNL3 are Cdc42 effectors targeting to the lamellipodium tip and shown here to nucleate and elongate actin filaments with complementary activities in vitro. In migrating B16-F1 melanoma cells, both formins contribute to the velocity of lamellipodium protrusion. Loss of FMNL2/3 function in melanoma cells and fibroblasts reduces lamellipodial width, actin filament density and -bundling, without changing patterns of Arp2/3 complex incorporation. Strikingly, in melanoma cells, FMNL2/3 gene inactivation almost completely abolishes protrusion forces exerted by lamellipodia and modifies their ultrastructural organization. Consistently, CRISPR/Cas-mediated depletion of FMNL2/3 in fibroblasts reduces both migration and capability of cells to move against viscous media. Together, we conclude that force generation in lamellipodia strongly depends on FMNL formin activity, operating in addition to Arp2/3 complex-dependent filament branching.

Suggested Citation

  • Frieda Kage & Moritz Winterhoff & Vanessa Dimchev & Jan Mueller & Tobias Thalheim & Anika Freise & Stefan Brühmann & Jana Kollasser & Jennifer Block & Georgi Dimchev & Matthias Geyer & Hans-Joachim Sc, 2017. "FMNL formins boost lamellipodial force generation," Nature Communications, Nature, vol. 8(1), pages 1-16, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14832
    DOI: 10.1038/ncomms14832
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    Cited by:

    1. Stephen M. Coscia & Andrew S. Moore & Cameron P. Thompson & Christian F. Tirrito & E. Michael Ostap & Erika L. F. Holzbaur, 2024. "An interphase actin wave promotes mitochondrial content mixing and organelle homeostasis," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Franziska Lehne & Thomas Pokrant & Sabnam Parbin & Gabriela Salinas & Jörg Großhans & Katja Rust & Jan Faix & Sven Bogdan, 2022. "Calcium bursts allow rapid reorganization of EFhD2/Swip-1 cross-linked actin networks in epithelial wound closure," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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